Preparation of articles having a contact biocidal property

ABSTRACT

In a process for the preparation of an article having a contact biocidal property, there is provided a polymer solution which contains atomic/metallic silver in suspension or complexed with the polymer and/or which contains a silver compound in solution, in suspension or complexed with the polymer. This polymer solution is applied to a substrate by impregnation or surface deposition, thus coating the substrate. Alternatively, it is possible to convert the polymer solution to a fibre, film, powder or foam, effectively forming the article from the polymer solution instead of coating an existing article. In either case, any silver compound present is reduced to atomic/metallic silver, and the resultant article is dried. 
     Chitosan is preferably used as the polymer, although poly(vinyl alcohol) and sodium alginate can also be used. The polymer may be cross-linked at a suitable point in the process to insolubilize it.

This invention relates to the preparation of articles having a contactbiocidal property derived from atomic or metallic silver disperseduniformly through the articles or through a surface coating on thearticles. The articles having the contact biocidal property have a widerange of applications, especially in the health care and associatedindustries. Articles prepared according to the invention have acharacteristic that effectively kills a wide range of micro-organismswhich come in contact with the articles.

It is known that atomic/metallic silver is a highly effective contactbiocide. U.S. Pat. Nos. 5,817,325 and 5,849,311 give examples of theapplication of an organic coating to a substrate followed by immersionof the coated substrate in a bath containing a silver salt. U.S. Pat.No. 4,960,413 describes the production of a wound dressing by immersionof chitosan-containing fungal fibres, or non-woven material preparedfrom them, in silver nitrate solution.

The invention provides a process for the preparation of an articlehaving a contact biocidal property, the process comprising the steps of

-   -   (a) providing a chitosan solution which contains atomic/metallic        silver in suspension or complexed with the chitosan and/or which        contains a silver compound in solution, in suspension or        complexed with the chitosan,    -   (b) either applying the chitosan solution to a substrate by        impregnation or surface deposition or converting the chitosan        solution to a fibre, film, powder or foam,    -   (c) reducing the silver compound, if present, to atomic/metallic        silver, and    -   (d) drying the resultant article.

It is preferred that the chitosan solution provided in step (a) containsatomic/metallic silver. Such a chitosan solution may be prepared byreducing an aqueous solution or suspension of a silver compound toatomic/metallic silver by chemical or photochemical means andsubsequently dissolving the chitosan in the resultant suspension. Analternative preparation comprises admixing an aqueous solution of thechitosan with an aqueous solution or suspension of a silver compound andsubsequently reducing the silver compound to atomic/metallic silver bychemical or photochemical means. Alternatively, the chitosan solutionmay be prepared by slurrying chitosan with a soluble silver salt toprepare a chitosan/Ag⁺ complex, dissolving the chitosan/Ag⁺ complex in asuitable aqueous acid and photochemically reducing the silver ions inthe chitosan/Ag⁺ solution to atomic/metallic silver. The photochemicalreduction may be effected earlier in the process, which then comprisesslurrying chitosan with a soluble silver salt to prepare a chitosan/Ag⁺complex, photochemically reducing the silver ions in the chitosan/Ag⁺complex to atomic/metallic silver, and dissolving the chitosan/Ag°complex in a suitable aqueous acid.

The chitosan solution provided in step (a) may, however, contain asilver compound in solution, in suspension or complexed with thechitosan. In this case it is necessary to perform step (c) after step(b) of the process.

Although chemical reduction is possible, photochemical reduction ispreferred for reasons of practicality. In this case it is advantageousto convert any soluble silver salt, for example silver nitrate or silverperchlorate, to one of the relatively insoluble and highlyphotosensitive silver halides (chloride, bromide or iodide, or mixturesof these) before exposure to ultraviolet/visible light.

Depending on the intended end use, it may be desirable to insolubilisethe chitosan after step (b) by crosslinking or other means. This may beeffected immediately after. step (b), after step (c) if that step isperformed, or during or after step (d).

In step (b) of the process of the invention, the chitosan solution iseither applied to a substrate by impregnation or surface deposition orconverted to a fibre, film, powder or foam. Application to a substrate,particularly a fibrous substrate, is preferred. The fibres may beorganic, inorganic or metallic fibres or blends of these. The fibres ofthe substrate may be loose fibres or form sliver, rove, yarn, woven orknitted fabric, non-woven material including paper products, or garmentsmade from any of these. Preferred fibres include cotton or othercellulose-based natural or man-made fibres (e.g. viscose rayon), wool orother protein-based fibres, and polyamide, polyester, polyolefin (e.g.polypropylene), polysaccharide and carbon fibres. Other usable fibresinclude those made from alginic acid and its salts, polyacrylic acid andits salts, poly(methacrylic acid) and its salts, or carboxymethylcellulose and its salts or mixtures thereof either with each other orwith the fibres previously mentioned. The fibrous substrate may be givenadditional chemical or physical treatment(s) prior to or subsequent tothe application of the silver/chitosan coating. The substrate mayalternatively be a film, foam or membrane or an article formed from afilm, foam or membrane. The film, foam or membrane may, for example, becomposed of cellulose, polyamide, polyester, poly(tetrafluoroethylene)or a related polymer in which one or more of the fluorine atoms in themonomer has (have) been replaced by chlorine atom(s), polyacrylic,polypropylene, alginic acid or its salts, polyacrylic acid or its salts,poly(methacrylic acid) or its salts, carboxymethyl cellulose or itssalts, or carragheenan. Deposition of the chitosan solution on thesubstrate may be carried out by padding, printing, spraying or pressureimpregnation. An alternative to application of the polymer solution to asubstrate is to convert the chitosan solution into fibre, film, foam orpowder by the techniques normally used for these conversions,effectively forming the article from the polymer solution instead ofcoating an existing article. In this case the atomic/metallic silverwill be present throughout the article rather than concentrated in asurface layer.

The process according to the invention effectively dispersesatomic/metallic silver through the article or through a surface coatingon the article in such a way that the silver substantially or whollyretains its biocidal properties. The concentration of silver in thechitosan solution can be adjusted accurately to the required valuebefore deposition on the substrate (or conversion of the chitosansolution into fibre, film, foam or powder), so ensuring a precise andreproducible level of treatment with the minimum waste of expensivesilver compounds. This accurate control of the silver concentration isnot possible with methods involving immersion of the article in a bathcontaining a silver compound. The inclusion of the silver in thechitosan solution before application to the substrate (or conversion ofthe chitosan solution into fibre, film, foam or powder) is an essentialfeature of the invention and reduces the number of stages in theprocess.

For most applications it is desirable to have the silver present wholly(or as nearly so as is practicable) as atomic/metallic silver. In thisform it is insoluble and will not be leached out, so that the articlewill retain its biocidal properties. However for some applications itmay be desirable to have a proportion of the silver present either as asoluble salt or as a relatively insoluble salt with a finite, but verylimited, aqueous solubility. The precise nature and composition of thesilver in the coating will depend on the ionic species present in, orintroduced into, the reaction process, the pH, and the extent ofreduction.

The invention is illustrated by the following Examples.

EXAMPLE 1

A 2% solution of chitosan [DA=0.16] in 0.2 M lactic acid was preparedand 100 ml of this solution mixed with 0.68 g AgNO₃ dissolved in 50 ml0.1 M lactic acid. A sample of cotton fabric was padded with this togive ˜110% pick-up, then oven-dried at 45° C. The fabric graduallydeveloped a grey colour on exposure to light, indicating thatphotochemical reduction was taking place.

EXAMPLE 2

A 2% solution of chitosan [DA=0.16] in 0.2 M lactic acid was preparedand 100 ml of this solution mixed with 0.68 g AgNO₃ dissolved in 50 ml0.1 M lactic acid. A solution of 0.25 g NaCl in 10 ml distilled waterwas run in slowly with stirring to give a white opaque suspension ofAgCl in chitosan. This was padded on to a sample of polyester/cottonblend fabric, the sample dried at 45° C., then neutralised in 2% NH₄OHsolution, rinsed and developed photochemically by UV irradiation.

EXAMPLE 3

Chitosan [DA=0.16] (11 g) was dissolved in 900 ml 0.1 M acetic acid andfiltered to remove insoluble material. The filtered solution was stirredwhile a solution of 4.25 g AgNO₃ in distilled water was added. Oncemixed, a solution of 1.61 g NaCl in 100 ml 0.1 M acetic acid was addedto give a rapid precipitation of finely dispersed AgCl which graduallychanged from white to a purplish grey, indicating photochemicalconversion of the silver species present from Ag⁺ to Ag°. This was thendeveloped by irradiating with uv/visible light, while stirring, tofurther reduce the Ag⁺ photochemically.

Three samples of cotton fabric were padded with this solution toapproximately 100% pickup, dried, then reduction was completedchemically by (a) steeping in a bath containing hydroquinone/sodiumhydroxide/sodium metabisulphite, rinsing and drying; (b) treating at 90°C. in a bath containing D-glucose/sodium hydroxide, rinsing and drying;(c) treating at 90° C. in a bath containing D-glucose/sodium carbonate,rinsing and drying.

The three samples, together with a control sample of cotton fabricpadded with chitosan containing no silver, were tested for antibacterialactivity against methicillin-resistant Staphylococcus aurus NCTC 4163using the SNV 195 924 method. All three silver-containing samples showedGrade 1 antibacterial activity, a 100% kill with a 2 mm zone ofinhibition. The control sample showed only Grade 4 (partial)antibacterial kill.

EXAMPLE 4

Chitosan [DA=0.16] (2.5 g) was dissolved in 900 ml 0.1 M acetic acid andfiltered to remove insoluble material. The filtered solution was stirredwhile a solution of 4.0 g AgNO₃ in 25 ml distilled water added slowly,care being taken to ensure that it is well mixed during the addition.Then a solution of 1.38 g NaCl in 25 ml distilled water was added andthe mixture stirred in the presence of light to bring aboutphotochemical conversion of the silver species present from Ag⁺ to Ag°.A 300 ml portion of the suspension was taken and stirred while anadditional 2.25 g of chitosan, dampened with methanol to aid itsdispersion, was added, followed by 0.75 ml glacial acetic acid. A sampleof cotton was padded with this solution to approximately 110% uptake,dried and sent for testing for antibacterial activity againstmethicillin-resistant Staphylococcus aurus NCTC 4163 using the SNV 195920 qualitative plate test and the quantitative SNV 195 924 test. Thesample showed Grade 1 antibacterial activity “with good effect and withpronounced inhibition zone”, in the first test, and very impressive andhighly significant antibacterial activity in the second test.

EXAMPLE 5

A 100 ml portion of a chitosan/silver mixture containing 0.5 g chitosanand 0.4 g “silver” in 0.1 M acetic acid was produced as described inExample 3 and mixed with 100 ml of a 0.5% chitosan solution, also in 0.1M acetic acid. A sample of cotton was padded with this solution toapproximately 110% uptake, dried, and sent for testing for antibacterialactivity against methicillin-resistant Staphylococcus aurus NCTC 4163using the SNV 195 920 qualitative plate test and the quantitative SNV195 924 test. The sample showed Grade 1 antibacterial activity “withgood effect and with pronounced inhibition zone”, in the first test, andvery impressive and highly significant antibacterial activity in thesecond test.

EXAMPLE 6

A sample of chitosan (2 g) was dissolved in 400 ml 0.1 M acetic acid,filtered and stirred while a solution of 0.8 g AgNO₃ in 10 ml distilledwater was added. Stirring was continued while the mixture was beingirradiated with uv/visible light until it was converted to apurplish-grey colour. A portion of this mixture was diluted to twice thevolume then padded onto a sample of activated carbon fibre to give 145%uptake. The sample was oven-dried at 50° C., neutralised in diluteammonia, rinsed well and oven-dried again. This was sent for testing forantibacterial activity against methicillin-resistant Staphylococcusaurus NCTC 4163 using the SNV 195 920 qualitative plate test. The testshowed that there was no zone of inhibition, i.e. no diffusion of anyantibacterial ingredient from the coating into the culture medium, butzero growth underneath, i.e. 100% kill of all bacteria on contact.

EXAMPLE 7

A portion of the undiluted chitosan/silver solution prepared in Example7 was placed in an ASL 500 home spray container and sprayed onto asample of cotton fabric to effect treatment on one side of the fabriconly.

EXAMPLE 8

Chitosan (8 g) was dissolved in 400 ml 0.2 M acetic acid, filtered toremove any insoluble particles, and stirred while a solution of 0.8 gAgNO₃ in 10 ml distilled water was added. Stirring was continued whilethe mixture was being irradiated with uv/visible light until it wasconverted to a purplish-grey colour. A further 32 g chitosan flake wasadded, mixed well in, then 10 ml glacial acetic acid added while thethickening solution was stirred. The viscous mass was let stand for 24hours, then used to print on a range of fabrics: a) a 100% cottonfabric; b) a 70:30 cotton:polyester blend fabric; c) an activated carbonfibre fabric; d) a 100% alginate fibre fabric; e) a 80:20alginate:viscose blend fabric.

1. A process for the preparation of an article having a contact biocidalproperty, the process comprising the steps of (a) providing a chitosansolution which contains a silver compound in solution, a silver compoundin suspension or a chitosan/Ag⁺ complex, (b) applying the chitosansolution to a fibrous substrate by impregnation or surface deposition,(c) reducing the silver compound to atomic/metallic silver, and (d)drying the resultant article, steps (b) and (c) being performed ineither order and step (d) being performed after step (b) and before orafter step (c).
 2. A process according to claim 1 wherein the chitosansolution contains atomic/metallic silver, which is prepared by reducingan aqueous solution or suspension of the silver compound toatomic/metallic silver by chemical or photochemical means andsubsequently dissolving the chitosan in the resultant suspension.
 3. Aprocess according to claim 1 wherein the chitosan solution containsatomic/metallic silver, which is prepared by admixing an aqueoussolution of the chitosan with an aqueous solution or suspension of thesilver compound and subsequently reducing the silver compound toatomic/metallic silver by chemical or photochemical means.
 4. A processaccording to claim 1 wherein the chitosan solution containsatomic/metallic silver complexed with the chitosan, which is prepared byslurrying chitosan with a soluble silver salt to prepare a chitosan/Ag⁺complex, dissolving the chitosan/Ag⁺ complex in a suitable aqueous acidand photochemically reducing the silver ions in the chitosan/Ag⁺solution to atomic/metallic silver.
 5. A process according to claim 1wherein the chitosan solution contains atomic/metallic silver complexedwith the chitosan, which is prepared by slurrying chitosan with asoluble silver salt to prepare a chitosan/Ag⁺ complex, photochemicallyreducing the silver ions in the chitosan/Ag⁺ complex to atomic/metallicsilver, and dissolving the chitosan/Ag^(°) complex in a suitable aqueousacid.
 6. A process according to claim 1 wherein the chitosan solutionused in step (b) contains a silver compound and step (c) is performed bychemical or photochemical means.
 7. A process according to any one ofclaims 2-6 in which the photochemical reduction of the silver compoundis effected after converting the silver compound to a silver halide. 8.A process according to any one of claims 2-6 further comprisingcrosslinking the chitosan after step (b).
 9. A process according to anyone of claims 2-6 further comprising crosslinking the chitosan afterstep (c).
 10. A process according to any one of claims 2-6 furthercomprising crosslinking the chitosan after step (d).
 11. A processaccording to any one of claims 2-6 further comprising crosslinking thechitosan during step (d).
 12. A process according to claim 1 wherein thechitosan solution is applied to a substrate comprised of organic,inorganic or metallic fibres or blends of such fibres.
 13. A processaccording to claim 12 in which the fibres of the substrate are loosefibres or form sliver, rove, yarn, woven or knitted fabric, non-wovenmaterial including paper products, or garments made from any of these.14. A process according to claim 12 or claim 13 wherein the fibres areselected from the group consisting of cotton or other cellulose-basednatural or man-made fibres, wool or other protein-based fibres, orpolyamide, polyester, polyacrylic, polyolefin, polysaceharide or carbonfibres, fibres made from alginic acid and its salts, fibres made frompolyacrylic acid and its salts, fibres made from poly(methacrylic acid)and its salts, and fibres made from carboxymethyl cellulose and itssalts, or mixtures thereof.